Non-additive interactions of nucleobases in model dinucleotide steps occurring in B-DNA crystals

Abstract

Non-additivity of base-base interactions in all ten possible model dinucleotide steps were analyzed on MP2/aug-cc-pvDZ quantum chemistry level. Selected conformations of four nucleobases exactly matched to ones occurring in B-DNA crystals. In most of 162 analyzed tetramers both threeand four-body contributions are negligible except of d(GpG) steps. However, in these dinucleotides both contributions are always of opposite signs and in all cases the sum of all non-additive part of intermolecular interactions do not exceed 2.6 kcal/mol. This stands for less than 5% of the overall binding energy of dinucleotide steps. Also replacements of guanine with 8-oxoguanine in d(GpG) systems introduces non-additivity of the same magnitude as for canonical dinucleotides. It is observed linear relationships between values of the total binding energy obtained in the tetramer basis set and estimated energy exclusively in dimers basis sets with assumption of pairwise additivities. For all analyzed dinucleotides steps there are also linear correlations between amount of non-additive contributions and magnitude of pairs interactions. Based on differences in electrostatic contribution to the total binding energy of four nucleobases and polarity of dinucleotide steps three distinct classes of dinucleotide steps were identified.Response to Reviewers: 1) I recommend to do a careful proofreading, there are many typos and some sentences are difficult to understand. Thank you. Careful proofreading was applied and text was modified accordingly.2) Page 3, Results and discussion Alltogether 162 dinucleotide steps were analyzed. The number of individual steps is variable, why is it so? Why there was 48 d(GpG) steps, but only 10 d(GpC) steps? What were the PDB codes of structures from which steps were chosen, and which steps (chain ID, res ID) were chosen? What was the resolution of these structures? This information could go to the Supplementary material.In supplementary material details related to analyzed structures are provided now. The differences in dinucleotide populations have strictly technical reason. Since in my previous work accepted for publication in Int.J.Quantum Chem. (DOI:10.1002/qua.22435) detailed analysis of d(GpG) steps were presented I have just included these data in this work. Consequently this dinucleotide is overrepresented. Since it constitutes its own class I do not think that such overrepresentation changes papers conclusions. On the other hand it is not necessary extending the number of other dinucleotide steps since the non-additivity is quite small and they were selected from broad range of data according to IIE and structural parameters diversities.3) Page 3, Results and discussion The numbers of steps are large enough to perform some statistical analysis of resulting energies. E.g. ANOVA could be performed to test whether the mean energies in dinucleotide steps differ significantly each from other. Also, is the distribution of energies for individual steps Gaussian or not? If not, some non-parametric ...

A computational proposal for the experimentally observed discriminatory behavior of hypoxanthine, a weak universal nucleobase

“…There has been discussion in the recent literature regarding the additivity of interactions between nucleic acid bases. 68,77,[84][85][86] In the present situation, we anticipate that any errors in our additivity assumption of the individual interactions energies are small. Indeed, recent work has carefully considered the additivity of interactions in model dinucleotide steps in B-DNA crystals containing natural and/or modified bases, and determined that the pairwise additivity simplification can be reliably applied as a first approximation without the necessity of energy calculations on the entire complex.…”

Structural and energetic consequences of oxidation of d(ApGpGpGpTpT) telomere repeat unit in complex with TRF1 protein

“…Only most representative sets of structures were used for precise intermolecular interaction energies (IIE) estimation at DF-MP2/aug-cc-pvDZ (aDZ) level of theory using MolPro package [54]. Since dinucleotide steps comprising stacked guanine molecules can exhibit significant non-negligible many-body contributions [35,36] all IIE values were corrected using linear relationships proposed elsewhere [56]. In all cases where quantum chemistry calculations were applied the simplified model was used in which sugar-phosphate backbones were replaced with hydrogen atoms.…”

“…As it was previously demonstrated [34][35][36] interactions in d(GpG) dinucleotide steps can exhibit significant non-additive character reaching several kcal mol -1 . Furthermore, manybody contributions to stabilization of dinucleotide steps comprising 8-oxoguanine are also non-negligible [56]. Fortunately, sum of all many body terms scale linearly with non-additive part and simple correction is possible.…”

“…Histogram plots for all distributions were supplied in edges of corresponding axis Fig. 4 Regression analysis between intermolecular interactions in dinucleotide steps estimated using pair-wise additivity (IIE(additive)) and full inclusion of all many body contributions (IIE(total)) [56] Fig. 5 Distributions of intra-strand stacking interactions in CTT of analyzed oligomers.…”

“…Figure 4. Regression analysis between intermolecular interactions in dinucleotide steps estimated using pair-wise additivity (IIE(additive)) and full inclusion of all many body contributions (IIE(total))[56].…”